The Weeks Post Transplant #2

The mistake happened, the recovery was wrenching and worrisome, and the Holidays were emotional.   Looking back, it’s hard to comprehend how we got through it.  But looking forward, Hope continues.

On Day +1, the symptoms and side-effects from the high dose chemotherapy he received the previous week surfaced. Theofanis’ counts dropped to zero, the mouth sores appeared, and Theofanis was feeling miserable. For the first time in six months, Theofanis’ eyelashes started growing back and an even fuzz surfaced on his scalp, a sign that his stem cells from his first transplant were working hard. But  Eleni and Kosta knew that this phenomenon was temporary and all this new hair would disappear once again.  Over the course of the next week, Theofanis experienced a very difficult time. He began to have an irregular heartbeat which the doctors determined was caused by the antifungal medicine he had been on since the first transplant. The remedy was simple…stop the antifungal. The mucositis this time around was far, far worse than what he experienced before. There were more and bigger mouth sores that continued down his throat.  There were signs that the mucositis inflamed his entire digestive tract. He had blood in his urine which was caused by the inflamation in his bladder and urethra. Concerns over bacterial infections surfaced so he was pumped with more prophylactic medicines. But every culture came back negative, so finally an ultrasound of his bladder confirmed it was mucositis. The pain medicine he was on, a form of morphine called dilaudid, caused severe itching. His skin began to slough off, too. The only true remedy to his misery would be his stem cells engrafting.

Theofanis couldn’t eat of course, he didn’t feel like playing Wii, he didn’t want to read, and he didn’t want to do anything. Another thing he didn’t do was complain. “The first transplant was easier than I thought it would be, and the second transplant is a lot harder than I thought it would be,” Theofanis told him mom and dad. Of course there were tears, mostly due to his pain. But, he once again showed incredible resolve.

Then, exactly one week to the day of his stem cell rescue, his white counts unexpectedly appeared at 0.1. “It’s still really at zero,” they would say. “Let’s see what happens tomorrow.” Then on Day +8, his counts jumped to 0.3. They were going up! They were definitely going up! No one expected this. It was a reason to celebrate in addition to the events that followed that morning:

THE CROSS OF CHRIST’S CRUCIFIXION

A week or so prior, Theofanis’ godmother, Evy, had heard that a priest from Greece is travelling the US with a piece of Christ’s cross which has been known to heal the sick. And this piece of the cross was nearby at the monastery in Wisconsin where streams of visitors poured into the monastery on a daily basis to be blessed by it. Evy contacted the monastery and told the gerontisa (head nun) about Theofanis. Within days, the Yianases received a call from the monastery with news that the priest would bring the cross to Theofanis and bless him in the hospital. So, the morning of day +8, the gerontisa and Father Ioannis from Crete brought the holy cross to Comer. And their beloved Father Andrew came as well. Breaking all the rules, Eleni and Kosta told the staff that Theofanis was having visitors. And with a WBC of 0.3, they were not allowing anyone to argue with them.  This was a special visit, and the doctors and nurses knew it, too.

There was also another special thing occurring that morning. A special bond has been developing between the Yianases and two other Greek families--a bond created by a beast called neuroblastoma. Three young Greek boys in the Chicago area are fighting this cancer. These three boys were each diagnosed in the month of May, in three consecutive years: Yano was diagnosed May of 2009, Stathi was diagnosed in May of 2010, and Theofanis was diagnosed in May of 2011. Yano is done with treatment and is in remission. . Stathi just completed treatment, but with a few nasty spots that are presenting themselves on scans, is considered to have stable disease. And, of course, Theofanis is in active battle. Rene (Yano’s mom) and Carly (Stathi’s mom) have been an inspiring source of information, support and therapy for Eleni. So Eleni told them that Father Ioannis was coming to Comer to bless Theofanis, and the three moms agreed that it would be wonderful to have all three boys blessed under the same roof.

Father Andrew arrived first and visited with Theo and Kosta while Eleni was awaiting the arrival of the others.  Father Ioannis and the head nun arrived with the cross and headed to the hospital chapel to bless Yano and Stathi.  They then made their way to Theo's room where Theofanis welcomed them with a smile. Father Ioannis took a medium-sized silver cross out of a wooden box. (The piece of Christ’s cross was embedded in the silver cross.) Father Ioannis placed the cross over Theofanis and moved it across Theo's body, from head to abdomen, to limbs.  He then pulled a piece of the cotton from the case that protected the cross, gave it to Theofanis, and told him to keep it.  He also put his hand on Theofanis’ head, leaned in to him and told him that he’s going to be fine, and he expects him to come to Crete to visit him and buy him a cup of coffee when he’s a little older. Theofanis smiled again.  And as Eleni and Kosta thanked Father Ioannis and gerontisa for coming, they told them that Father Ioannis himself lost his two-year old son to cancer. It was then that he came into possession of the cross and decided to take it to those who were sick and needed healing. Father Ioannis looked at Kosta and Eleni and told them that he understands exactly what they are going through. Then, he comforted them by telling them that Theofanis will be fine! Everything is going to be ok! So the comfort that these people brought to Theofanis and his family and the hope that Christ’s cross will deliver the miracle they have been seeking was truly a precious gift and blessing!

The next day, early in the morning after Theo’s labs were drawn, the Resident came in to wake up Eleni and show her the results of Theo’s blood test. With a big smile on her face, she handed the report to Eleni which showed that Theo’s WBC was 1.6 and his Absolute Neutrophils appeared at 1,216! She told her that it was incredible that his counts were so high. She said all the doctors are shocked and extremely happy. Then the resident said, “I heard you had a big ceremony here yesterday,” inferring that the hospital staff was thinking divine intervention may have contributed to the incredible news that Theo’s new stem cells have taken over, faster and stronger than anyone ever expected. And actually, his stem cells engrafted faster than during his first transplant even!  Mid morning, Dr. Cohn came in with an entourage of residents, gave Theo a huge smile and said, “Your mom is right, you really do have super cells!”

So the next few days, Eleni and Kosta watched his counts skyrocket each day and saw his mucositis ease a bit.  But, they also watched Theofanis catch a cold. Well, he really didn’t catch a cold, but the cold symptoms surfaced. Remember, tests showed that Theofanis had the rhinovirus colonies in his sinuses, that had the potential of turning into a cold. Well, now that his stem cells came back and his immunity was restarted, his new cells discovered the nasty rhinovirus and decided to start fighting it. So, the sneezing, runny nose and fever began. Although he was on a clear path to recovery,  the hope that he would be released in time for Christmas fizzled.  

HAPPY BIRTHDAY JESUS AND HAPPY BIRTHDAY THEOFANIS!

After coming to grips with the fact that Theo would not be allowed out of the hospital, the Yianas family had to plan a Christmas and Birthday celebration unlike any other year. Kosta and Eleni were determined to make sure this Christmas was just as magical and just as happy, just in a different place.  And the way that they were going to do it was to make sure their family was together.  Fortunately, Dr. Cohn was the attending physician that week on the 6th Floor of Comer, so she gave the ok to have Theo’s sisters visit him that day. And with that approval, Eleni and Kosta broke all the rules! 

On Christmas morning, Santa delivered the Yianas family’s gifts to both Palatine and Comer Children’s Hospital. Two sets of stockings were filled with goodies, two Christmas trees were surrounded by presents, and two iPads were working hard as Kosta and Theofanis were Facetiming from Chicago and Eleni, Demetra and Sophia were Facetiming from Palatine. The family opened Christmas presents together via video. Each sibling would take their turn opening presents while the others waited anxiously to see what Santa brought them. All three kids knew that they were very, very good this past year, so they hoped that Santa would bring them everything they wanted!  It took nearly two hours to open all the gifts, which was an indication that yes, the Yianas kids were very, very good kids!

So Eleni packed up the Honeybaked ham, gathered the party supplies and balloons and with a birthday cake in hand, headed to the hospital to celebrate Christmas and Theofanis’ 7^th birthday! When they arrived at the hospital, with the help of the Tunney family, they set up a mini birthday party in the lobby of the 6^th floor of Comer. (As mentioned, the Yianases decided to break a lot of rules that day!)

Wearing a mask, Theofanis emerged from his room for the first time in over three weeks! He saw familiar, loving faces, heard them sing “Happy Birthday” to him, and even joined them in a board game. After blowing out the candles on his cake through his mask (he had to lift one side of it to get any air out), Theofanis showed off his overly-decorated hospital room (again, breaking more rules) where everyone was shocked to see the piles and piles of toys and gifts from Comer’s Child Life department and from his nurses. Plus, there were gifts from his teachers, family and friends! So to the many generous people who sent cards and gifts and texts and wishes filled with love, you helped turn a worrisome Christmas Day into a special day that was filled with smiles and laughter. 

OUR PROMISE TO FIND A CURE

As everyone recalls, the wonderful parish of St. Demetrios in Elmhurst held the Taste of Greece Fall Glendi in Theofanis' honor in late September, with the proceeds to benefit Theo and neuroblastoma research.  The church left it up to the Yianas family to decide which research program to donate to. The Yianases chose to donate to the University of Chicago neuroblastoma research program lead by Dr. Cohn. And, they chose a program specific to a new therapy that not only has proven to help children who have relapsed, but also has the potential in the future to help newly diagnosed patients who are undgeroing front-line therapy. Dr. Cohn is leading the development of an MIBG therapy room which delivers radioactive isotopes to neuroblastoma cells to kill only those cells. It is a therapy that requires children to be isolated in a lead-lined room for an entire week while radiation is continuously being delivered.   The MIBG program at the University in Chicago would be the only one in Illinois and Indiana, and one of the very few in the United States that could offer this treatment to their patients. Plus, invaluable research on MIBG therapies have the potential to lead to better and more effective treatments with less toxicity. As Theofanis’ pediatrician and aunt has said, “what if they could attach chemotherapy drugs to MIBG isotopes and deliver chemo to only the neuroblastoma cells and spare healthy cells?” It’s a brilliant idea. Those are the kinds of ideas that spur research that will one day find the desperately needed cure.

So, Theofanis asked Dr. Cohn to come to his room at 637 Comer on the day he was being discharged to home.  Dr. Cohn arrived and was surprised to see a beaming Theofanis, check in hand, announce that he wanted to donate to help children with Neuroblastoma.  She was very happy and thankful for the donation and the Yianas’ support of the MIBG therapy program which is opening in 2012.  So to everyone who attended the Glendi, donated to the Glendi, and who volunteered their time, especially those who spent endless hours planning and organizing, the Yianas family thanks you, Dr. Cohn and the researchers at the University of Chicago thank you, and Theofanis thanks you. And you all should feel proud that your efforts will help many children in the future fight this terrible disease.

DISCHARGE, DEFIANCE AND HOME

On December 30^th, when discharge day finally arrived, Kosta packed everything up, all the cards, the posters, the decorations and the Christmas tree,  and waited for Eleni to pick them up.  Dr. Cunningham had asked the Yianas family to head to the Ronald McDonald House as they did last time, but Kosta and Eleni felt that it was better to be home over the New Years holiday.  Theo would be more comfortable there and he would have less exposure to other people.  Knowing what it was like the first time around, they insisted their home was cleaner, Theo would try to begin eating, and he would be happier sleeping in his own bed and playing freely with his sisters. The doctors, now used to dealing with Kosta and Eleni’s defiance to the rules, highly recommended that they stay close to the hospital during the first few days after discharge. “We’ll drive fast if we have to come to the ER,” they told them, and they signed the discharge documents, thanked all the nurses, waved goodbye and headed home!

GETTING STRONGER EVERY DAY

He’s feeling good. He’s comfortable. He’s laughing. He’s shooting baskets. He’s jumped in the snow. He’s playing with his sisters and arguing with them too. Theo's task now is to slowly get back into his "normal" routine of eating more, tackling homework, studying with his tutor, and exercising to get his strength back.  He was off of his liquid nutrition, TPN, about a week after discharge.  He was experiencing some issues with his gastrointestinal system during his last week in the hospital, and an astute nurse pointed out to the doctors that he was going through morphine withdrawal. So, he was weaned off the narcotic while at home. His regular visits to the clinic (two per week) for a checkup and labs showed his recovery was going well and his blood counts look good. So Dr. Cunningham reduced his visits to once a week and now to every two weeks. The smiles from the doctors during Theo’s visits to the hospital also confirm Theofanis is recovering extremely well!

So, Theofanis has finally passed the half-way point of his treatment. Chemo Induction Therapy is done. Tumor resection is done. Stem Cell Transplants are done. Now, the next step is Radiation Therapy. And Eleni and Kosta need to decide what’s the safest path for their son.

How did it happen?

Still reeling from the simply unbelievable mistake the doctors made when administering more chemotherapy than necessary, the Yianas family sought to find a reason for the error.  The trust that was once unshakeable is now damaged.  Eleni and Kosta, though terribly disappointed, wanted to be sure that, going forward, they could be able to trust the doctors at the University of Chicago with their son's care and that measures would be taken to prevent another lapse in communication that could put their son in harm’s way.

How did this happen exactly?  Eleni was with Theo during the first three days of his high dose chemotherapy.  Each morning, she documented and watched the medical team hang his two chemo bags that were each infused over a period of 24 hours and the one chemo syringe injection. She asked the name, dosage, and duration of each drug, and she knew that the responses she would get would be the same as the previous day. Nothing was unusual, nor out of the ordinary. The Yianases had a copy of the protocol for the second round of the COG clinical trial specific for a Tandem Transplant. They knew that Carboplatinum, Etoposide and Melphalan were the drugs and the dosages were high. They knew that Theo would be given 3 days of one drug and 4 days of the other two. They knew that their son’s exact dosage was calculated based off his weight and some other factors. They knew there would be side effects that would eventually kick in and linger until his new stem cells could take over.

But, on the third day of chemo, after his medicine was given and the doctors and nurses left Theofanis’ room, Eleni felt nervous and uneasy. She stared at the chemo bags that were adorned with “caution” and “poison” labels. She concentrated, though on the label that captured her son’s name followed by an endless list of numbers and formulas that resembled algebraic calculations. Not fully understanding what she was reading and accepting that pharmacists speak an entirely different language, a feeling came over her. A bad feeling.  As she nervously rummaged through Theo’s Stem Cell Transplant Binder which contained every document pertaining to her son’s treatment, Theofanis noticed her changed demeanor. And when Eleni dragged her 10-lb binder to his IV pole and held it up to his chemo bag, he asked what she was doing. “Just double-checking something, sweetheart.”  She pulled up the protocol and read the pharmaceutical calculation guidelines that Theo was on. She didn’t understand what she was reading. She looked at the chemo bags. She looked at the protocol document. She was looking, but wasn’t sure what she was looking for. Her bad feeling did not go away. Then, Eleni pulled out her laptop, searched her files, and located the 200-page pdf file of the complete Children’s Oncology Group Neuroblastoma Treatment Protocol. She searched for the treatment protocol for children undergoing a Single Stem Cell Transplant. In other words, she searched the protocol that her child was NOT on.  Filtering through the pharmaceutical guidelines for the variable dosing factors (such as adjustments for body mass vs. kidney function loss vs. other possible factors for variance), Eleni found the page of the protocol that she believed her son would be on IF he were only doing one transplant. She held her laptop up to Theo’s IV pole, and she saw every single number jump off of her computer screen and onto the labels of her son’s chemo bags. Every single number on those bags matched the protocol that her son was NOT on. She was punched in the stomach with sickness and stabbed in the heart with panic.  The numbers were all higher.

Eleni called for then nurse and then called Kosta, who was on his way to Comer to “switch” shifts with her. There’s something wrong. There’s something terribly wrong, she told him. Kosta arrived in Theo's room to see Eleni very worried and hurriedly double-checking the protocol worksheets.  A few moments earlier, Eleni was in the pressurized entry way of Theo’s room with the nurse reviewing the formal orders in Comer’s computer system. The nurse insisted Theo was getting the right dose because it was exactly what was written in the orders. Nonetheless, she contacted Reggie, the Pharmacist, who also confirmed he mixed that exact medicine that’s written in the orders. But, when Eleni showed the nurse the COG protocol on her laptop, the nurse stared at the screen, looked at Eleni, and then immediately paged both Dr. Cunningham, Dr. Cohn and the attending, Dr. Uma. “I hope you all think I’m crazy and am freaking out for no reason,” she told the nurse. “I pray to God you all think I’m crazy.” The nurse looked at her, worriedly.

“Get Dr. Cohn, get Dr. Cunningham, get Reggie, get them here now!” she insisted.  “The orders in the computer are wrong! You are overdosing my child!”

Kosta and Eleni demanded that doctors immediately ascertain whether or not the dosage was, in fact, incorrect.  Dr. Cunningham, nor Dr. Cohn were in the building. The other doctors, nurses and pharmacists gathered behind closed doors of a conference room.  Eleni and Kosta sat patiently and calmly in Theo’s room because moments earlier, Theo asked, “What’s going on?” And there was no way they were going to allow their son to worry about anything.  After a short time that felt like an eternity, Reggie came into Theo’s room. Eleni and Kosta stood up, and simply asked, “Is it wrong?” And Reggie looked them in the eyes and said, “Yes, it’s wrong.” He confirmed that Theofanis was overdosed on high dose chemotherapy.

“Then why aren’t you stopping that pump right now?”

“It’s too dangerous to stop it now,” he said.

Here’s the plan…the two drugs that were scheduled for the fourth day will be amended to about half the prescription so that cumulatively he will get the correct total dosage.  However, the Melphalan had already been given in full.  There was no remedy for this.  Theo received about thirty percent more Melphalan than he was supposed to.

As the reality of the erroneous chemotherapy infusion began to be realized, Eleni and Kosta were gripped with fear for their son -- virtually the same feeling they felt when Theofanis was first diagnosed in early May.  How could this happen and why?  Who could have made such a careless error?  But most importantly, what does this mean? What will happen to Theofanis, short-term and long-term?

Dr. Cunningham, who is directly overseeing Theofanis’ care during transplant, arrived shortly thereafter, and told Eleni and Kosta that he took full responsibility for the mistake. But, before confirming that the original chemotherapy orders were wrong, he said, “Theo was not poisoned.” He assured that Theo was going to be ok.  “But, thank goodness you caught the mistake, Mrs. Yianas.” What of the Melphalan, then, Dr. Cunningham?  He proceeded to tell Mom and Dad that Melphalan is highly effective at killing neuroblastoma cells.  It also hits the bone marrow hard and suppresses white blood cell production. So,  Theo's recovery will take longer than expected, and the short-term side effects included more aggravated mucositis.  He said there were no long-term side effects from this drug. Eleni and Kosta listened to Dr. Cunningham, but could no longer trust a word he said.

Yes, trust was gone, and Dr. Cunningham knew it.

“Do you know how we feel right now?” they asked him. Their fear quickly shifted to anger and determination to find answers.   As the Section Chief of Oncology, he took full responsibility.  He admitted that he made the mistake. But, how did this happen?  Who was really responsible? An investigation began, with all the formalities associated when overdosing a child. Root cause needs to be identified, reports need to be written, reviews by committees, etc.  Plus, how does this affect Theo’s status with the Children’s Oncology group now that the protocol was violated? Is he off trial? The one thing though that the Yianas’ knew for a fact was that the “failsafe” system of multiple checkpoints and verification that each chemotherapy order should follow, failed. It supposedly failed for the first time…with their son. “You are a world-class institution. How do you allow this to happen?” Kosta demanded.  No one had a response for him.

Over the next few days, Dr. Cunningham, Dr. Cohn, and Dr. Panigrahi, along with the residents and other fellows received sharp questions and follow-up questions on everything they were doing.  They were reminded that the trust that the Yianas’ had in them had been extensively damaged, and this was not the first time there was a communication issue amongst their ranks.  Yet, this certainly was the most blatant, and was close to being disastrous. As the Yianases continued to experience different emotions, they quickly realized that the most important thing they had to do was not allow Theo to see or sense any mistrust with the hospital, doctors or staff. So, Eleni and Kosta put on happy, optimistic faces each time the doctors came in.

Then, on the Day of Theo’s Stem Cell Rescue, Day Zero, they requested a sit-down meeting with Dr. Cunningham and Dr. Cohn. A meeting where the Yianases asked these doctors if they are willing to work with them on rebuilding trust. The Yianases took the following position:

1. The first step in regaining trust is having access to information. The Yianases asked for full disclosure: the formal investigation report, plus documentation of the medicines Theofanis was given with the dosages he was given.
2. For the remainder of Theo’s treatment, they asked that someone sit down with them and highlight the full COG protocol and identify every area of treatment and dosing, so that they could double-check what every doctor or nurse does.
3. They demanded that no one criticize or complain that they are asking too many questions.  In the past, Eleni and Kosta were told that some folks on the hospital staff thought they asked too many direct questions. Some people didn’t like being watched while they were drawing their son’s blood or while changing their son’s dressing or while changing and cleaning his IV lines. In the past, Eleni and Kosta sensed how some doctors or staff would be annoyed by their redundant questions.  

Dr. Cunningham and Dr. Cohn fully agreed to their requests. And most importantly, they agreed that Theo’s health and recovery is everyone’s top priority.

Then, Eleni asked each of the doctors: “What does your gut tell you about the effects that this mistake will have on Theo?” Dr. Cohn said, “Thank goodness you caught the mistake.” In early clinical trials, children were given the full dosages of the three chemotherapies and it proved to be highly toxic to the children. Then she said something that they heard before: Melphalan is highly effective against Neuroblastoma. That little extra dose may help.  Then, Dr. Cunningham said that he too thinks that the Melphalan will specifically target Neuroblastoma. And he said short-term, Theo’s bone marrow will take longer to recover.

Eleni ended the meeting by telling them that she and Kosta don’t want their relationship or their discussions with them to be argumentative or confrontational. The doctors expressed their appreciation with that. And, she told them both, “I’m kicking myself for not double-checking the protocol on the first day.” Then, Dr. Cohn shook her head and said, “I’m kicking myself.” You see, Dr. Cohn, Theofanis’ primary oncologist and the hospital’s top Neuroblastoma expert, steps away and turns primary care over to Dr. Cunningham and the Stem Cell Transplant team during this phase of treatment. Dr. Cohn did not review the orders. The Yianas’ believe that if she saw the orders, she would have caught the error. And they think she believes the same thing.   

So, what happened? The official investigation summary and report will be complete by end of January. Eleni and Dean were promised copies of it. Apparently, templates for this clinical trial were created and entered into Comer’s computer system a year ago. All current orders are drafted using these templates.  (By the way, these templates were created in order to prevent a mistake like this from ever happening.)  And because Theofanis was the first child at Comer to move forward with two stem cell transplants, the template was used for the first time with him. So, who created the incorrect templates? Dr. Cunningham said he did.

The doctors are sorry.  While at first, it seemed they were frantic and defensive, Kosta and Eleni do know they are sincere in their apologies. What happened was not good for Theo, nor them. Both Dr. Cohn and Dr. Cunningham conveyed that this never happened to either of them before. They had to admit error to the Children’s Oncology Group and to their peers.  Their reputations have been affected. But more so, their patient was placed in harm’s way, and for that, they are very, very sorry.

So, Day Zero of Theo’s second Stem Cell Rescue began with a new understanding of the care and attention the Yianas Family expects their son must receive.  It began with commitment from the oncology team that they will be forthcoming with information. And it began with uncertainty on Theo’s short term recovery. You see, his counts dropped to zero and the signs of side-effects began to surface.